Solubility measurements can, in principle, provide detailed information on the "instantaneous" structure and kinetic properties of intracellular water. In practice, the potential of this approach has been unfulfilled because of technical problems and the complicating presence of cellular membranes. Reference phase (RP) analysis and cryomicrodissection, developed in this laboratory, are helping to ameliorate these difficulties. Experiments with this system have disclosed an unusual nuclear water property: reduced solvency for pentoses and hexoses. Selective exclusion of monosaccharides has not been reported for the water of any non-living aqueous system. It appears to arise from water's modified structure in the ground substance, which is imposed by the nuclear cytomatrix. The proposed research is directed toward exploring several questions raised by this discovery. 1) What does selective monosaccharide exclusion disclose about the "instantaneous" structure of nuclear water? 2) How is intracellular water differentiated spatially with respect to monosaccharide exclusion? 3) What cytomatrix elements play a role in modifying water? 4) How are intracellular water's solvent properties modified during physiological and developmental change? Answers are being sought by application of current cryomicrodissection and RP technology to several developmental stages in Rana pipiens oocytes and by developing new RP-based approaches to studying somatic cells (Aplysia ganglia and Myxicola axons) in vivo and cell isolates in vitro.